Autosomal dominant polycystic kidney disease has an incidence of approximately 1/1000, and accounts for approximately 10% of end-stage reanl disease. While the basic defect causing one form of APKD, has eluded biochemical and physiological detection, there has been substantial progress in mapping the PKD-1 gene. Isolation of the gene and characterization of the basic defect(s) would lead to better understanding of the etiology and pathogenesis of the disease. The long-term goal of this project is to clone and characterize the PKD-1 gene, and its product. To this end, we will use a highly efficient method of scanning genomic DNA from the interval around PKD-1 for expressed sequences. Expressed sequences recovered by exon trapping will be analyzed by genetic and molecular methods for the presence of the PKD-1 gene. Candidate clones will be analyzed by comparative sequence analysis from normal and affected individuals.